OSCR

Laser interstitial thermal therapy enhances bidirectional blood-brain barrier permeability in glioblastoma.

Overview

Authors: Ryan T Cleary1, Yiwei Fu1,2, David Giles1, Jinyun Yuan1, Diogo P Moniz Garcia1, Danny Palmer3, Rowland H Han1, Timothy Woodiwiss1, Alicia B Yang4, Dimitrios Mathios1,5, Hong Chen1,5,6, Albert H Kim1,5
ORCID iDs: Ryan T Cleary, David Giles, Jinyun Yuan, Danny Palmer, Rowland H Han, Timothy Woodiwiss, Alicia B Yang, Dimitrios Mathios, Hong Chen, Albert H Kim
  1. Taylor Family Department of Neurosurgery, WashU Medicine, St. Louis, Missouri, USA
  2. The Department of Musculoskeletal Oncology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
  3. University of Denver, Denver, Colorado, USA
  4. Icahn School of Medicine at Mount Sinai, New York, New York, USA
  5. The Brain Tumor Center at Siteman Cancer Center, St. Louis, Missouri, USA
  6. Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA
Institutions: The First Affiliated Hospital, Sun Yat-sen University (China); University of Denver (United States); Icahn School of Medicine at Mount Sinai (United States); Washington University in St. Louis (United States)
Journal: Neuro-oncology, volume 28, issue 7, pages 1649-1661
Dates: received 14 October 2025; accepted 9 April 2026; published online 13 April 2026; in print July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1093/neuonc/noag080 · PMID 41981754 · PMCID PMC13338339 · OpenAlex W7154462673
Open access: hybrid, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), human (organism), mouse (organism), other condition (population), clinical / translational (subfield)
Methods: Statistics
Keywords: caveolae-mediated transcytosis, ctDNA, glioblastoma, laser interstitial thermal therapy
MeSH: Blood-Brain Barrier*, Brain Neoplasms*, Capillary Permeability*, Glioblastoma*, Laser Therapy*, Animals, Endothelial Cells, Humans, Mice, Mice, Inbred C57BL, Transcytosis (* major topic)
Topic: Ultrasound and Hyperthermia Applications (Biomedical Engineering, Engineering), according to OpenAlex
Funding: Schnucks Fund; Sally Jungclaus Fund; Siteman Cancer Center; Duesenberg Family Fund
Citations: cited by 1 paper (Europe PMC); 41 references in the paper

Abstract

Background: Laser interstitial thermal therapy (LITT) is a minimally invasive treatment for glioblastoma that increases blood-brain barrier (BBB) permeability. However, the mechanisms and spatiotemporal features of this effect remain unclear. It is also unknown whether LITT promotes release of circulating tumor DNA (ctDNA).

Methods: Using our previously developed LITT mouse model, we employed single-cell RNA-sequencing (scRNA-seq) to investigate gene expression changes in endothelial cells following LITT in the naive mouse brain. Brains were also harvested at multiple time points to assess LITT effects on tight junction (TJ) integrity and transcytosis via immunofluorescence and transmission electron microscopy. Human glioblastoma tissues were analyzed to monitor ambient caveolae-mediated transcytosis in tumor regions. Finally, ctDNA levels in mouse plasma were quantified using digital-droplet PCR following LITT.

Results: LITT triggered downregulation of pathways related to cell-cell junctions and upregulation of transcytosis. LITT transiently disrupted TJ integrity for 7 days up to 100 µm away from the ablation zone. Further, LITT increased caveolae-mediated transcytosis in endothelial cells for 21 days, peaking at 14 days, in part due to suppression of the transcytosis inhibitor Mfsd2a. LITT facilitated ctDNA detection in mouse plasma at 1 h, 3 days, 7 days, and 14 days post-procedure.

Conclusions: Our study demonstrates that LITT transiently disrupts the BBB in the periphery of the ablation with endothelial TJ disruption and transcytosis upregulation following distinct time courses. LITT effects on the BBB are bidirectional and enhance ctDNA release in addition to enabling brain entry of agents.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

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Data

Datasets cited

Data Availability

scRNAseq data deposited to GEO (accession number GSE329855 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329855)).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 12 authors, 4 keywords, 11 MeSH terms, 4 funders, 41 references.

Cite

This paper

Cleary, R. T., Fu, Y., Giles, D., Yuan, J., Moniz Garcia, D. P., Palmer, D., Han, R. H., Woodiwiss, T., Yang, A. B., Mathios, D., Chen, H., & Kim, A. H. (2026). Laser interstitial thermal therapy enhances bidirectional blood-brain barrier permeability in glioblastoma. Neuro-oncology, 28(7), 1649-1661. https://doi.org/10.1093/neuonc/noag080

BibTeX

@article{cleary2026laser,
author = {Cleary, Ryan T and Fu, Yiwei and Giles, David and Yuan, Jinyun and Moniz Garcia, Diogo P and Palmer, Danny and Han, Rowland H and Woodiwiss, Timothy and Yang, Alicia B and Mathios, Dimitrios and Chen, Hong and Kim, Albert H},
title = {{Laser interstitial thermal therapy enhances bidirectional blood-brain barrier permeability in glioblastoma}},
journal = {Neuro-oncology},
year = {2026},
month = jul,
volume = {28},
number = {7},
pages = {1649--1661},
publisher = {Oxford University Press},
issn = {1522-8517},
doi = {10.1093/neuonc/noag080},
url = {https://doi.org/10.1093/neuonc/noag080},
pmid = {41981754},
pmcid = {PMC13338339}
}

RIS

TY - JOUR
AU - Cleary, Ryan T
AU - Fu, Yiwei
AU - Giles, David
AU - Yuan, Jinyun
AU - Moniz Garcia, Diogo P
AU - Palmer, Danny
AU - Han, Rowland H
AU - Woodiwiss, Timothy
AU - Yang, Alicia B
AU - Mathios, Dimitrios
AU - Chen, Hong
AU - Kim, Albert H
TI - Laser interstitial thermal therapy enhances bidirectional blood-brain barrier permeability in glioblastoma
T2 - Neuro-oncology
J2 - Neuro Oncol
PY - 2026
DA - 2026/07/01
VL - 28
IS - 7
SP - 1649
EP - 1661
SN - 1522-8517
PB - Oxford University Press
DO - 10.1093/neuonc/noag080
UR - https://doi.org/10.1093/neuonc/noag080
LA - en
ER -

CSL-JSON

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